Knowledge of metabolism of chloroalkanes is essential for understanding their toxicity. Many chloromethanes and -ethanes have recognized toxicity; their metabolism and its role in toxicity has been studied. Similar claims cannot be made for chloropropanes. The purpose of this project is to study chloropropane metabolism. Inasmuch as metabolism involves removal of chlorine from the chloropropane, the proposed studies begin with development of a method to measure metabolically-produced chloride in incubations of chloropropanes with rat liver cell fractions. Sufficiently sensitive measurement is possible with the chloride-selective electrode, which will be used to monitor chloride concentration resulting from chloropropane metabolism. Chloride from sources other than chloropropane metabolism will be minimized, so that metabolically-produced chloride can be detected. Proposed studies will continue with application of the chloride measurement method to a variety of chloroethanes and -propanes. Measurement of dechlorination of chloroethanes enables comparison of the chloride electrode method to previous studies in which chloride released from 36Cl-chloroalkanes was measured radiometrically. Dechlorination of chloropropanes is an index of total metabolism; measurement of dechlorination of various chloropropanes enables structure of chloropropanes to be related to their metabolism + dechlorination rates. Dechlorination rate in microsomal (cytochrome P-450) vs. cytosolic (glutathione transferase) incubations is an indication of the relative capacities of these two metabolic routes; the relationship of these capacities to chloropropane structure will be examined. Finally, proposed studies include organic metabolite identification. Dechlorination rates and putative metabolic schemes will be used as the basis for selection of some of the 29 chloropropanes for metabolite identification studies. Metabolites will be produced in cell fraction incubations and identified by high-performance liquid chromatography of derivatives. Measurement of metabolites will enable comparison of metabolite production rate with chloride production rate, suggesting the extent to which chloride production is an index of total metabolism. In addition, identification of metabolites enables confirmation of theoretical metabolic pathways of the chloropropanes. Knowledge of metabolic rates and specific metabolites will be useful in selecting chloropropanes for toxicity studies and will be a basis for consideration of metabolism of more complex chloroalkyl compounds.